1. Field of the Invention
The invention is related with a polymer blend as an intermediate product for preparing nanoparticles, a process for preparing the polymer blend, a process for preparing nanoparticles and the nanoparticles obtainable by this process as well as method of treating patients with drugs or drug combinations adhered on or incorporated in nanoparticles.
2. Description of the Background
Nanoparticles in form of pseudolatex are derived from an oil-in-water submicron emulsion that is converted to colloidal polymer dispersion after removal of the organic solvent, used to dissolve the preformed polymer. Thus, they differ from most common latex prepared from water insoluble monomers by emulsion or dispersion polymerization. The major advantage of pseudolatexes relies upon the feasibility to convert most polymers into an organic colloidal dispersion allowing direct incorporation of plasticizers. Pseudolatexes of ethylcellulose in celluloseacetatephtalat have been used for pharmaceutical coating applications (Banker et al., Pharmaceutical Technology 1981, pp 55-61).
Nanocapsules of polylactide of size centered around 220 nm were reported Amnoury in J. Pharm. Sci., 1990, pp 763-767. The nanocapsules were prepared by an interfacial deposition technique. This method was applied for encapsulation of indomethacin.
Nanoencapsulation of low molecular weight antibiotic in polylactide-glycolide material was reported by Julienne et al., Proceed. Intern. Symp. Control. Rel. Bioact. Mater., 1989, pp 77-78.
Bazile et al. reported in Biomaterials 1992, pp 1093-1102 about the preparation of nanoparticles of polylactide (90 to 250 nm) coated with albumin. The protein was used as stabilizer of the oil-in-water emulsion without mentioning any encapsulation of an active drug and its sustained release.
Gref et al. in Science 1994, 263, pp 1600-1603 have described the formulation of polylactide (or polycaprolactone)-polyethyleneglycol block copolymer in 140 nm pseudolatexes. The amphiphilic copolymers has been used to encapsulate low molecular weight compounds that are released in some hours in vivo.
Nanoparticles are used as drug delivery systems. In colloidal drug delivery systems, edited by Jorg Kreuter, Marcel Dekker, Inc., New York, Basel, Hong Kong, pp 219-341, the significance of nanoparticles is described as well as conventional methods for producing such nanoparticles. Biodegradable pseudo-latex particles (nanoparticles) have been prepared from biocompatible polyesters by conventional emulsification/solvent diffusion methods. The coating polymer is initially dissolved in a water immiscible chlorinated organic solvent (or in mixtures of chlorinated and more polar solvents). Size of the particles usually exceeds 100 nm and no information is available about the effective encapsulation of especially protein drugs. Although, nanoparticles have been proven to be useful tools for drug delivery systems. Some problems relating to the control of particle size as well as particle loading with protein drugs are not solved. Also a high loading, a safeguarding drug activity and allowing for controlled drug release is a feature which is hard to match.